Dynamic covalent chemistry of peptides and epitope self-assembly

Dynamic means reversible under the reaction conditions. This is why this topic is entirely based on the concepts of supramolecular chemistry formulated by J.-M. Lehn. The difference lies in the aqueous solvent and the structural and functional complexity of the molecular targets. We use the bioorthogonal ligation of borylated epitopes with polyhydroxylated scaffolds to assemble numerically defined oligomers of amyloidogenic peptides, so-called miniamyloids.

Left: Lewis structure of a trimeric boroxole which tethers three prion protein epitopes PrP106-118. Right: A trimeric boronic ester of the Alzeimer Aβ32-40 peptide.

 

 

 

The ring-chain equilibria of cyclic peptide imines yields thermodynamic data about the macrocyclisation tendencies of linear peptide precursors.